Sign up to receive free email alerts when patent applications with chosen keywords are publishedSIGN UP

Abstract:

An improved phenylbutazone carrier composition provides increased
palatability to horses. Additionally, the composition improves the
bioavailability of the phenylbutazone and thus increases the horse's
blood plasma levels of the medicine for the same effective dosage of the
medicine.

Claims:

1. A phenylbutazone carrier composition for promoting consumption and
improving bioavailability of phenylbutazone to horses comprising:
phenylbutazone; and wherein the composition comprises, as a percentage of
the weight of phenylbutazone: about 2 percent artificial flavor; about
3.5 percent saccharine; about 1 percent aspartame; about 2 percent
sucralose; and about 2 percent of a carbonate salt or bicarbonate salt.

5. The composition of claim 1, further comprising an anti-caking agent.

6. A phenylbutazone carrier composition for improving the bioavailability
of phenylbutazone to horses comprising: phenylbutazone; and a salt
selected from the group consisting of carbonate salts and bicarbonate
salts added to the phenylbutazone in an amount of about 2 percent of the
weight of the phenylbutazone to improve bioavailability.

10. The composition of claim 6, further comprising artificial sweetener.

11. The composition of claim 6, further comprising artificial flavor.

12. The composition of claim 6, wherein the composition comprises, as a
percentage of the weight of phenylbutazone: about 4 percent saccharine;
between about 1 and 2 percent aspartame; artificial flavoring; and
anti-caking agent.

13. The composition of claim 12, wherein the composition further
comprises, as a percentage of the weight of phenylbutazone, between about
2 and 4 percent sucralose.

14. A phenylbutazone carrier composition for improving consumption and
increasing bioavailability in animals comprising: phenylbutazone; and,
for each 100 grams of phenylbutazone further comprising: about 2 grams of
an alkaline earth metal carbonate salt or alkaline metal bicarbonate
salt.

15. The composition of claim 14, further comprising artificial flavoring.

17. The composition of claim 14, further comprising artificial sweetener.

18. The composition of claim 17, wherein the artificial sweetener
comprises, for each 100 grams of phenylbutazone: between about 2 and 4
grams of sucralose; about 4 grams of saccharine; and between about 1 and
2 grams of aspartame.

19. The composition of claim 14, wherein the salt comprises, more
specifically, an alkaline earth carbonate.

Description:

PRIORITY

[0001] The present application is a continuation application of U.S.
application Ser. No. 12/608,913, filed Oct. 29, 2009, which is herein
incorporated by reference in its entirety, and which claims the benefit
of U.S. Provisional Application Ser. No. 61/227,282, filed Jul. 21, 2009,
which is herein incorporated by reference in its entirety.

THE FIELD OF THE INVENTION

[0002] The present invention relates to providing phenylbutazone to
horses. More specifically, the present invention relates to an improved
carrier formulation for delivery of phenylbutazone and functional
homologues thereof. The carrier is more palatable to horses than previous
phenylbutazone formulations and provides improved absorption into the
horse's blood stream.

BACKGROUND

[0003] Phenylbutazone, is one of the most popular and useful non-steroidal
anti-inflammatory veterinary pharmaceuticals. It is typically the drug of
choice for equine treatment when an illness or injury necessitates the
use of a painkiller or anti-inflammatory medication. Phenylbutazone
treats joint deterioration, swelling and inflammation from injuries,
founder, fevers, and various other pains experienced by horses.

[0004] While phenylbutazone has been used to treat horses for more than
thirty years, the administration of phenylbutazone persists in being the
source of many problems. Phenylbutazone has a bitter taste, and is thus
difficult to administer orally, but oral administration remains the
desired mode of administration. The horses often reject the bitter drug,
which leads to inconsistent dosages and difficulty in administering the
drug.

[0005] Phenylbutazone is typically available to horse owners and
veterinarians in one-gram tablets for oral administration. Horses do not
willingly eat phenylbutazone tablets. Absent physical force, most horses
will not swallow phenylbutazone tablets due to their bitterness. Thus,
administration of these tablets involves first catching the horse and,
depending on the individual personality and training of the horse,
applying various degrees of restraints. Restraints range from a halter to
prevent bobbing and weaving of the head, to more extreme measures that
prevent rearing and kicking.

[0006] Horse owners and veterinarians have developed several means for the
actual delivery of phenylbutazone to horses. In simple cases the tablets
are crushed and mixed with the horse's food. This method is problematic
because the crushed tablets do not adhere to the horse's food. Powder or
granules sift to the bottom of the feeder as the horse eats. The amount
of sifting varies with each administration and results in inconsistent
dosages or diet problems due to the addition of feed to administer the
remaining medication.

[0007] Some horses reject the grain and drug mixture altogether, requiring
the additional step of mixing the crushed tablet with syrup or molasses
before adding the bitter drug to the horse's feed. This method is
problematic for several reasons. Syrup and molasses are very sticky, and
the mixing process leaves a mess in the surrounding area as well as in
the mixing container and feed trough or dish. This can result in a loss
of medication and an inconsistent dose. In addition, the phenylbutazone
is insoluble in syrup and molasses making it impossible to obtain a
homogeneous mixture. If the mixture is not immediately administered to
the horse, the phenylbutazone settles resulting in an inconsistent dosage
or additional mixing requirements. Encapsulation of the crushed tablet
matter by the syrup or molasses also hinders the speed at which digestive
fluids can interact with the phenylbutazone and, consequently, blood
absorption of phenylbutazone is delayed through the digestive process.

[0008] The various method of administering phenylbutazone to horses are
unpleasant for the horse and the person, and can result in injury if the
person administering the drug is bitten, pawed or stepped on by a
stubborn horse. Because the medicine is bitter, a horse will continue to
reject the medicine with increasing intensity over time. Ultimately, it
becomes difficult or impossible to catch the horse three times a day for
delivery of the drug and, if caught, the horse attempts to reject the
medicine both before and after it is delivered.

[0009] The described administration problems with phenylbutazone would be
merely inconvenient, except that they, in turn, cause serious problems,
which are related to effective dosages. The drug is intended to control
potentially chronic inflammation and pain, which can result in permanent
soft tissue lesions, such as scarring of other fibroid tissue growth, as
a consequence of long term chronic inflammation cycles. The drug provides
relief from chronic cycles of inflammation and pain, and eventually
facilitates increased range of motion without permanent loss of function.
Thus, it is important to provide a method of administration that avoids
peaks and valleys in the blood concentration levels of phenylbutazone
arising from inconsistent dosage due to rejection or an inability to
catch the horse for administration of the drug.

[0010] An important factor to consider in the delivery of phenylbutazone,
in addition to methods for oral administration of the drug, is the speed
at which the drug is absorbed into the horse's blood. Inflammation and
pain are more easily relieved when effective treatment concentrations are
attained more quickly. This is especially true when the inflammation is
potentially associated with hemorrhaging due to soft tissue injury.
Maintaining the proper blood concentration level, timing, and diet are
critical to the effectiveness of the drug. Even so, it is commonly
understood that mixing a drug with a carrier, such as a nutritional base
for delivery of the drug, has the disadvantage of slowing down the blood
absorption rate.

[0011] While a veterinarian should make the determination on an individual
basis, a moderate dose for a 1000 pound horse is 1-2 grams or 5-10 cc per
administration. Oral administration of phenylbutazone is slow to take
effect, requiring 3-5 hours to achieve an effective concentration level.
Three dosages per day should be administered to maintain the proper blood
concentration level. However, due to the problems with oral
administration, most horse owners and veterinarians settle for a double
or sometimes only a single dosage per day, as opposed to the ideal triple
dosage. Administration and dosage problems are compounded where prolonged
treatments are required for treatment of chronic soft tissue injuries,
and these problems can result in significant health effects to the horse
and cost burden on the owner.

[0012] Some efforts have been made to improve the delivery of
phenylbutazone to horses. U.S. Pat. No. 6,022,563 describes carrier
formulations which ease administration of the medicine to the horse.
While the formulations provided improved the ability to induce the horse
to eat the medicine, there remained some difficulty in administering the
medicine to the horse. Additionally, the carrier formulations provided
showed little increase in the horse phenylbutazone blood concentration as
compared to pure phenylbutazone tablets. Because of the difficulty in
administering phenylbutazone and the rejection of the same by horses
discussed above, it would be desirable to have a more easily administered
formulation and to achieve increased blood concentrations in horses.

[0013] Therefore, there is a need for an improved carrier formulation of
phenylbutazone that is more palatable to horses than prior formulations,
that is easily administered in a proper dosage without special skills or
alteration from its manufactured state, and provides quicker absorption
into the bloodstream and increased blood concentrations.

SUMMARY OF THE INVENTION

[0014] It is an object of the present invention to provide an improved
phenylbutazone bearing formulation for administration to animals,
including horses.

[0015] The present invention overcomes the problems that are outlined
above and advances the art by providing an improved carrier formulation
for administering phenylbutazone in a palatable medium to horses. The
carrier formulation comprises a powdered carrier base including a
flavoring agent, a sweetener, and an anti-caking agent mixed with a
therapeutically effective amount of phenylbutazone. Additionally, the
present carrier formulation includes a buffer, helping to improve the
palatability and bioavailability of the drug. The present phenylbutazone
mixture is more palatable to horses than the prior art carrier
formulations, and also results in improved levels of phenylbutazone in
the horse's blood.

[0016] These and other aspects of the present invention are realized in a
phenylbutazone formulation as shown and described in the following
figures and related description.

BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Various embodiments of the present invention are shown and
described in reference to the numbered drawing wherein:

[0018] FIG. 1 shows a graph illustrating the blood levels of
phenylbutazone in a horse as achieved by the present invention.

[0019] It will be appreciated that the drawing is illustrative and not
limiting of the scope of the invention which is defined by the appended
claims. The embodiments shown accomplish various aspects and objects of
the invention. Similarly, not every embodiment need accomplish all
advantages of the present invention.

DETAILED DESCRIPTION

[0020] The invention and accompanying drawings will now be discussed in
reference to the numerals provided therein so as to enable one skilled in
the art to practice the present invention. The drawings and descriptions
are exemplary of various aspects of the invention and are not intended to
narrow the scope of the appended claims.

[0021] Phenylbutazone is known and is described in U.S. Pat. No.
2,562,830. Phenylbutazone is also known as
4-butyl-diphenyl-3,5-pyrazoidinedione, benzone, butadione, intrabutazone,
and numerous other common names. Phenylbutazone is widely understood to
be an effective veterinary anti-inflammatory and analgesic agent in
treating inflammation in horses and other animals.

[0022] According to the present invention, the phenylbutazone formulation
includes phenylbutazone, flavoring, anti-caking agent, saccharine,
aspartame, sucralose, and sodium bicarbonate or calcium carbonate. The
formulation is discussed in additional detail below.

[0023] The flavoring agent is an inactive ingredient, and is typically an
artificial flavoring. Flavor additives used in the flavoring agent may
also be products from a natural material. Although a variety of flavor
additives are palatable to horses including but not limited to, cinnamon,
strawberry, carrot, orange, or apple, it has found artificial green apple
flavoring, such as that which is commercially available from BFI
Innovations of Elgin, Ill. to be the most palatable to the broadest range
of horses.

[0024] Artificial sweeteners provide the advantage that, unlike natural
sugars, they do not promote significant tooth decay and contribute few if
any calories to the foods they sweeten. Additionally, it has been found
that the particular sweetener combination disclosed herein has improved
the palatability of the phenylbutazone formulation over the prior art
carrier formulations. The particular formulation disclosed herein has
been shown to improve the levels of phenylbutazone in a horse in addition
to improving the ease with which the phenylbutazone may be administered
to the horse.

[0025] Although beneficial, the anti-caking agent is not a necessary
ingredient to the carrier formulation of the present invention. The
anti-caking agent is utilized for the practical requirement of improving
the manufacturing process. The preferred anti-caking agent is silica
dioxide sold under the trade name Flogard, an example of which can be
purchased from Pharmatech Inc. The anti-caking agent improves the
manufacturing process by preventing clotting and balling of the product
typically caused by the tacky nature of the flavoring ingredients. It
should also be noted that, while the anti-caking agent silica dioxide is
added to the carrier formulation to improve manufacturing, some
additional anti-caking agents may present as sub-ingredients in some of
the flavoring ingredients. For example, calcium silicate is often found
as a sub-ingredient of the Fresh Green Apple flavoring ingredient.

[0026] The particular phenylbutazone formulation disclosed herein has
proved advantageous over prior art formulations. For example, while the
carrier formulation discussed in U.S. Pat. No. 6,022,563 shows a slightly
faster initial delivery speed as compared to pure phenylbutazone, the
'563 formulation shows rates of absorption and metabolization of the
phenylbutazone over subsequent intervals which is approximately
equivalent to that of delivery of pure phenylbutazone, resulting in
substantially the same biological effect of the phenylbutazone alone. The
present phenylbutazone formulation, however, shows improved delivery
speed as well as improved absorption and metabolism of the
phenylbutazone, resulting in higher blood concentrations as compared to
phenylbutazone tablets. Thus, the present formulation achieves improved
biological effectiveness of the phenylbutazone in addition to improved
ease of administration to the horse.

[0027] The respective ingredients of the carrier formulation are typically
provided as a solid, powder, or particulate at room temperature, so that
mixing of the materials results in a finely divided powder. The resulting
powder has an electrostatic affinity for the cellulosic substances that
horses eat, making it easier to mix the phenylbutazone composition into
horse feed.

[0028] The carrier formulation is produced by blending the ingredients to
achieve a homogeneous mixture. A suitable weight proportion of
phenylbutazone to achieve the advantages of the invention may be in the
range of 70% to 90% of the total formulation weight, with a more
preferable range being 85% to 90%. The formulation preferably has between
1% and 5% flavoring, about 3.5% saccharine, about 1% aspartame, and
between 1.8% and 3.6% sucralose.

[0029] The carrier formulation of the present invention is administered to
horse orally in its raw form or as a feed supplement by spreading it over
conventional feed components, including but not limited to, grain, hay,
oats, barley, corn and so on. Advantageously, the sweetener ingredients
typically provide the carrier formulation with an inherently tacky
property, such that the carrier formulation adheres to feed when it is
administered as a feed supplement. Thus, product is not lost due to
sifting as the horse eats. Horses consider that phenylbutazone delivered
with the carrier formulation as a treat, and they aggressively ingest it

Example 1

[0030] Example 1 describes a preferred product formulation for the present
invention, as well as the mixing and administration of the product.

[0031] During the first stage of preparation, seven individual batches of
product were mixed, each having a total weight of 115 kilograms. A 200
kilogram stainless steel blending mixer, commonly known in the art as a
V-shaped blender, was used to mix each batch. Before each batch was mixed
the blending mixer was sterilized by thoroughly wiping with a sterile
cloth soaked in rubbing alcohol. During the second stage of preparation,
the seven individual batches were combined and mixed in a 1000 kilogram
stainless steel V-shaped blending mixer to produce the finished product.

[0032] Each of the seven batches produced during the first stage of
preparation consisted of: 100 kilograms of phenylbutazone, 4 kilograms of
saccharine, 3 kilograms of Fresh Green Apple Flavor, 2 kilograms of
Aspartame, 2 kilograms of sodium bicarbonate, and 4 kilograms of FloGard.
The ingredients for a single batch were weighed and placed in the 200
kilogram blending mixer and blended for a period of 15 minutes. After 15
minutes of blending, the batch was removed from the 200 kilogram blending
mixer and weighed to confirm any product loss. An average of 2% was lost
do to coating the machinery. After weighing, the batch was placed into a
1000 kilogram blending mixer, but was not mixed until all seven batches
from the first stage of preparation were added to the 1000 kilogram
mixer.

[0033] During the second stage of production the seven batches were
blended in the 1000 kilogram blender for a period of 20 minutes to
produce 789 kilograms of finished product (accounting for the lost
material in blending in the first stage). After blending, the finished
product was removed and weighed to confirm any product loss.
Approximately 1% was lost. After weighing, the product was tested for
bacteria and continuity before packaging in individual doses. The
packaged product contained 1 gram of phenylbutazone, 0.04 gram of
Saccharine, 0.03 gram of Fresh Green Apple Flavor, 0.02 gram of
Aspartame, 0.02 gram of sodium bicarbonate, and 0.04 gram of FloGard, per
3.5 cc spoonful of powder.

Bioequivalence Test

[0034] The above product mixture was tested for bioequivalency as follows.
Three healthy mature geldings and two non-pregnant mares aged 3-15 years
with similar weights were chosen for a bioequivalence test. The
bioequivalence test was designed to determine the difference in blood
plasma absorption between commercially available phenylbutazone tablets
and the inventive product mixture described above.

[0035] Two weeks prior to the test, the horses did not receive any form of
medication; however, all horses were up to date on their vaccinations. At
five o'clock p.m. the evening before the test, each horse was fed a
normal meal consisting of 1 gallon of grain with fourteen percent
protein, and ten pounds of alfalfa hay. During the test each horse was
stabled separately and had access to drinking water at all times. On test
day, each horse was fasted until administration of the test product, and
then given a normal meal consisting of one gallon of grain with fourteen
percent protein and ten pounds of alfalfa hay five hours post dosing and
at twelve and one-half hours after administration.

[0036] The morning of the test, 4.60 grams of the product from example one
containing a total of four grams of phenylbutazone, was added to one half
gallon of grain with fourteen percent protein by lightly stifling. Each
horse was given 15 minutes to consume the grain. All five horses consumed
their grain during this allotted time. Each of the five horses followed
this procedure.

[0037] Two hours following administration a 4.5 cc blood sample was taken
from each of the five horses. Thereafter, additional 4.5 cc blood samples
were taken at half-hour intervals until the sixth hour. After the sixth
hour 4.5 cc blood samples were taken hourly until the eighth hour. After
the eighth hour 4.5 cc blood samples were taken at twelve and one-half
hours, sixteen hours, and eighteen hours. The blood samples were taken
with a 20 gauge one inch needle and promptly put into a green CST Lithium
Heparin tubes and cooled in ice water at 36 degrees F. When each sample
was collected, the blood sample was spun to separate the blood plasma
from each sample. The separated blood plasma was placed in a freezer for
twenty-four hours at 20 below zero.

[0038] After twenty-four hours, the blood plasma was thawed to room
temperature and phenylbutazone levels were quantified for each sample by
a validated HPLC method. The average phenylbutazone level for the five
horses at each of the sampling time intervals are given in FIG. 1.

[0039] Two weeks later after completing a wash out period, the same three
healthy mature geldings and two non-pregnant mares aged 3-15 years with
similar weights were used for a cross over bioequivalence test. This
bioequivalence test was to determine the concentration levels in blood
plasma absorption of commercially available phenylbutazone tablets.

[0040] Two weeks prior to the test, the horses did not receive any form of
medication, however all horse were up to date on their vaccinations. At
five o'clock p.m. the evening before the test, each horse was fed a
normal meal consisting of 1 gallon of grain with fourteen percent
protein, and ten pounds of alfalfa hay. During the test each horse was
stabled separately and had access to drinking water at all times. On test
day, each horse was fasted until administration of the test product (4
grams of crushed active ingredient phenylbutazone in tablets), and then
given a normal meal consisting of one gallon of grain with fourteen
percent protein and ten pounds of alfalfa hay five hours post dosing, and
at twelve and one-half hours after administration.

[0041] The morning of the test, four 1 gram tablets of the commercially
available phenylbutazone were crushed in to a fine powder, and were added
to one half gallon of grain with fourteen percent protein by lightly
stifling for each horse. Each horse was given 15 minutes to consume the
grain. None of the horses consumed their entire grain during this
allotted time. Each of the five horses followed this procedure.

[0042] Two hours following administration a 4.5 cc blood sample was taken
from each of the five horses. Thereafter, additional 4.5 cc blood samples
were taken at half-hour intervals until the sixth hour. After the sixth
hour 4.5 cc blood samples were taken hourly until the eighth hour. After
the eighth hour 4.5 cc blood samples were taken at twelve and one-half
hours, sixteen hours, and eighteen hours. The blood samples were taken
with a 20 gauge one inch needle and promptly put into a green CST Lithium
Heparin tubes and cooled in ice water at 36 degrees F. When each sample
was collected, the blood sample was spun to separate the blood plasma
from each sample. The separated blood plasma was placed in a freezer for
twenty-four hours at 20 below zero.

[0043] After twenty-four hours, the blood plasma was thawed to room
temperature and phenylbutazone levels were quantified for each sample by
a validated HPLC method. The average phenylbutazone level for the five
horses at each of the sampling time intervals are given in FIG. 1 as well
as in the following chart.

[0044] The following chart illustrates the blood plasma concentrations
achieved by Example 1 of the present invention as compared to pure
phenylbutazone and to the prior art phenylbutazone composition shown in
U.S. Pat. No. 6,022,563. This is instructive as the composition shown in
U.S. Pat. No. 6,022,563 was similarly administered to the horses in an
identical quantity as the present invention.

[0045] Example 2 describes another preferred product formulation for the
present invention, as well as the mixing and administration of the
product.

[0046] The product formulation for Example 2 was prepared in a manner
similar to that of Example. 1 but containing calcium carbonate. The
composition contained 100 kilograms of phenylbutazone, 4 kilograms of
saccharine, 3 kilograms of Fresh Green Apple Flavor, 2 kilograms of
Aspartame, 2 kilograms of calcium carbonate, and 4 kilograms of FloGard.

Bioequivalence Test

[0047] The formulation of Example 2 was tested for bioequivalency in a
manner similar to that of Example 1 as follows. Three healthy mature
geldings and two non-pregnant mares aged 3-15 years with similar weights
were chosen to determine the blood plasma absorption of product mixture
described above. Prior to the test, the horses did not receive any
medication. The evening before the test, each horse was fed a normal meal
which included of one gallon of grain and ten pounds of alfalfa hay.
During the test each horse was stabled separately and had access to
drinking water. On test day, each horse was fasted until given the
phenylbutazone formulation. Each horse was later given a meal of one
gallon of grain and ten pounds of alfalfa hay at five hours and at twelve
and one-half hours after administration of the phenylbutazone
formulation.

[0048] The morning of the test, 4.60 grams of the above phenylbutazone
product (containing four grams of phenylbutazone) was added to one half
gallon of grain. All five horses ate their grain during a 15 minute time
period. 4.5 cc blood samples were taken from each of the five horses at
2, 3, 4, 5, 6, 7, 8, 10, 12, and 18 hours. The blood samples were
promptly put into green CST Lithium Heparin tubes and cooled in ice
water. When each sample was collected, the blood sample was spun to
separate the blood plasma. The separated blood plasma was placed in a
freezer for twenty-four hours at 20 below zero.

[0049] After twenty-four hours, the blood plasma was thawed to room
temperature and phenylbutazone levels for each sample were measured by
HPLC. The average phenylbutazone level for the five horses at each of the
sampling time intervals are given in FIG. 1 as well as in the following
chart.

[0050] The following chart illustrates the blood plasma concentrations
achieved by Example 2 of the present invention as compared to pure
phenylbutazone and to the prior art phenylbutazone composition shown in
U.S. Pat. No. 6,022,563.

[0051] The Example 2 composition containing phenylbutazone with calcium
carbonate achieved blood plasma levels similar to those shown for
phenylbutazone with sodium bicarbonate in Example 1. The phenylbutazone
composition of Example 2 achieves blood plasma levels which are
significantly higher than those achieved by prior phenylbutazone
compositions which did not contain calcium carbonate, such as that shown
in U.S. Pat. No. 6,022,563 to Gordon.

[0052] U.S. Pat. No. 6,022,563 discloses a formulation that provides
slightly faster and more complete uptake than pure phenylbutazone when
both are placed by tube directly into the horse's stomach. It can be
observed that the present invention achieves a significantly higher and
longer lasting blood concentration of phenylbutazone than the '563
composition, even through the testing of present invention relies on the
horse to eat the composition while the '563 patent placed the entire dose
into the horse via tube. The present testing results also show the
dramatic improvement of the present invention as compared to requiring
the horse to eat pure phenylbutazone. The horses discontinued eating and
did not intake the full dose of phenylbutazone.

[0053] Additional compositions of a phenylbutazone formulation according
to the present invention are provided here to illustrate the preferred
ranges of the present invention. For example, a batch may contain 100
grams of phenylbutazone, 2 grams of green apple flavoring, 2 grams of
anti caking agent, 4 grams of saccharine, 1 gram of aspartame, 2 grams of
sucralose, and 2 grams of sodium bicarbonate or calcium carbonate.

[0054] Alternatively, an effective batch of medicine may also contain 100
grams of phenylbutazone, 4 grams of green apple flavoring, 2 grams of
anti caking agent, 4 grams of saccharine, 1 gram of aspartame, 4 grams of
sucralose, and 2 grams of sodium bicarbonate or calcium carbonate. These
formulations are understood to perform equally to that disclosed above.

[0055] It is thus observed that the present invention preferably contains,
for each 100 grams of phenylbutazone, between about 2 and 4 grams of
flavoring, about 4 grams of saccharine, between about 1 and 2 grams of
aspartame, between about 0 and 4 grams of sucralose, about 2 grams of
sodium bicarbonate or calcium carbonate, and between about 2 and 4 grams
of an anti caking agent. This results in a composition of between about
85.5 and 88.5 percent phenylbutazone, between about 1.8 and 3.4 percent
flavoring, between about 3.4 and 3.5 percent saccharine, between about
0.8 and 1.7 percent aspartame, between about 0 and 3.4 percent sucralose,
between about 1.7 and 1.8 percent sodium bicarbonate or calcium
carbonate, and between about 1.7 and 3.5 percent anti caking agent. It
will be appreciated that the percent composition may be trivially altered
by adding inert ingredients to the above compositions without departing
from the present invention.

[0056] FIG. 1 presents a chart illustrating the results of the
bioequivalency tests discussed above. As is observed, the compositions of
Example 1 and Example 2 achieved an approximate 250 percent increase in
the blood plasma concentration of phenylbutazone as compared to
phenylbutazone alone. Both of these results were based on the horse
eating the medicine along with food. As discussed, the present invention,
even when the horse is required to eat the medicine, achieved significant
increases in both the intensity and duration blood phenylbutazone levels
as compared to the prior art medicine disclosed in the '563 patent which
was administered completely to the horse by tube. The inventor believes
that this may be due to several factors. It is believed that the
particular carrier formulation promotes the uptake of phenylbutazone into
the horse, increasing not only the speed but also the efficiency of
uptake. It is believed that both the particular combination of
sweeteners, as well as the addition of sodium bicarbonate or calcium
carbonate may thus improve the uptake of the phenylbutazone.

[0057] As the present formulation provides a significant increase in the
blood plasma concentrations of phenylbutazone two desirable outcomes may
be achieved. If a person doses the same amount of phenylbutazone to a
horse, the resulting blood plasma levels will be higher and will last
longer, improving the effectiveness of the medicine in treating the
horse. Alternatively, if it is not desired to increase the resulting
blood plasma levels, a lower dose may be provided to the horse while
maintaining the same blood plasma levels. As phenylbutazone has been
observed to cause some gastrointestinal discomfort or damage, this may
reduce any such negative effects. Additionally, lowering the dose will
reduce the cost and effort associated with treating a horse.

[0058] There is thus disclosed an improved phenylbutazone composition. It
will be appreciated that numerous changes may be made to the present
invention without departing from the scope of the claims.